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Article: MAD2-induced sensitization to vincristine is associated with mitotic arrest and Raf/Bcl-2 phosphorylation in nasopharyngeal carcinoma cells

TitleMAD2-induced sensitization to vincristine is associated with mitotic arrest and Raf/Bcl-2 phosphorylation in nasopharyngeal carcinoma cells
Authors
KeywordsBcl-2
MAD2
Nasopharyngeal carcinoma
Raf
Vincristine
Issue Date2003
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2003, v. 22 n. 1, p. 109-116 How to Cite?
AbstractMitotic arrest deficient 2 (MAD2) is thought to be a key component of the mitotic checkpoint, which ensures accurate chromosome segregation. Reduced expression of MAD2 protein is associated with mitotic checkpoint abrogation and chromosomal instability in certain types of human cancers. To explore the possibility of developing a novel strategy for the treatment of cancer based on selective killing of mitotic checkpoint-defective or -competent cells, here we have investigated the effect of MAD2 expression on cellular sensitivity to checkpoint-targeting anticancer drugs. We reintroduced MAD2 protein in a mitotic checkpoint-defective nasopharyngeal carcinoma cell line, CNE2, using an inducible expression vector. We found that overexpression of MAD2 led to an increased sensitivity to vincristine, which was accompanied by increased mitotic index and G2/M cell cycle arrest. In addition, increased phosphorylation of Raf, MEK1/2 and Bcl-2 was observed in MAD2-overexpressing cells in response to vincristine. Furthermore, inhibition of phosphorylation of MEK1/2 by its inhibitor PD098059 led to reduced sensitivity to vincristine, which was associated with decreased Bcl-2 phosphorylation. Our data suggest a role for MAD2 in the sensitization of cancer cells to certain mitotic checkpoint-targeting anticancer drugs.
Persistent Identifierhttp://hdl.handle.net/10722/67637
ISSN
2015 Impact Factor: 7.932
2015 SCImago Journal Rankings: 4.047
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWang, Xen_HK
dc.contributor.authorJin, DYen_HK
dc.contributor.authorWong, HLen_HK
dc.contributor.authorFeng, Hen_HK
dc.contributor.authorWong, YCen_HK
dc.contributor.authorTsao, SWen_HK
dc.date.accessioned2010-09-06T05:56:54Z-
dc.date.available2010-09-06T05:56:54Z-
dc.date.issued2003en_HK
dc.identifier.citationOncogene, 2003, v. 22 n. 1, p. 109-116en_HK
dc.identifier.issn0950-9232en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67637-
dc.description.abstractMitotic arrest deficient 2 (MAD2) is thought to be a key component of the mitotic checkpoint, which ensures accurate chromosome segregation. Reduced expression of MAD2 protein is associated with mitotic checkpoint abrogation and chromosomal instability in certain types of human cancers. To explore the possibility of developing a novel strategy for the treatment of cancer based on selective killing of mitotic checkpoint-defective or -competent cells, here we have investigated the effect of MAD2 expression on cellular sensitivity to checkpoint-targeting anticancer drugs. We reintroduced MAD2 protein in a mitotic checkpoint-defective nasopharyngeal carcinoma cell line, CNE2, using an inducible expression vector. We found that overexpression of MAD2 led to an increased sensitivity to vincristine, which was accompanied by increased mitotic index and G2/M cell cycle arrest. In addition, increased phosphorylation of Raf, MEK1/2 and Bcl-2 was observed in MAD2-overexpressing cells in response to vincristine. Furthermore, inhibition of phosphorylation of MEK1/2 by its inhibitor PD098059 led to reduced sensitivity to vincristine, which was associated with decreased Bcl-2 phosphorylation. Our data suggest a role for MAD2 in the sensitization of cancer cells to certain mitotic checkpoint-targeting anticancer drugs.en_HK
dc.languageengen_HK
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/oncen_HK
dc.relation.ispartofOncogeneen_HK
dc.subjectBcl-2en_HK
dc.subjectMAD2en_HK
dc.subjectNasopharyngeal carcinomaen_HK
dc.subjectRafen_HK
dc.subjectVincristineen_HK
dc.subject.meshAntineoplastic Agents, Phytogenic - pharmacologyen_HK
dc.subject.meshCalcium-Binding Proteins - physiologyen_HK
dc.subject.meshCarrier Proteinsen_HK
dc.subject.meshCell Cycle Proteinsen_HK
dc.subject.meshFungal Proteins - physiologyen_HK
dc.subject.meshHumansen_HK
dc.subject.meshMitogen-Activated Protein Kinases - metabolismen_HK
dc.subject.meshMitosis - drug effectsen_HK
dc.subject.meshNasopharyngeal Neoplasms - pathologyen_HK
dc.subject.meshNuclear Proteinsen_HK
dc.subject.meshPhosphorylationen_HK
dc.subject.meshProto-Oncogene Proteins c-bcl-2 - metabolismen_HK
dc.subject.meshProto-Oncogene Proteins c-raf - metabolismen_HK
dc.subject.meshTumor Cells, Cultureden_HK
dc.subject.meshVincristine - pharmacologyen_HK
dc.titleMAD2-induced sensitization to vincristine is associated with mitotic arrest and Raf/Bcl-2 phosphorylation in nasopharyngeal carcinoma cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0950-9232&volume=22&issue=1&spage=109&epage=116&date=2003&atitle=MAD2-induced+sensitization+to+vincristine+is+associated+with+mitotic+arrest+and+Raf/Bcl-2+phosphorylation+in+nasopharyngeal+carcinoma+cellsen_HK
dc.identifier.emailJin, DY:dyjin@hkucc.hku.hken_HK
dc.identifier.emailWong, YC:ycwong@hkucc.hku.hken_HK
dc.identifier.emailTsao, SW:gswtsao@hkucc.hku.hken_HK
dc.identifier.authorityJin, DY=rp00452en_HK
dc.identifier.authorityWong, YC=rp00316en_HK
dc.identifier.authorityTsao, SW=rp00399en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/sj.onc.1206069en_HK
dc.identifier.pmid12527913-
dc.identifier.scopuseid_2-s2.0-0037427074en_HK
dc.identifier.hkuros80460en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0037427074&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume22en_HK
dc.identifier.issue1en_HK
dc.identifier.spage109en_HK
dc.identifier.epage116en_HK
dc.identifier.isiWOS:000180166900012-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridWang, X=7501854829en_HK
dc.identifier.scopusauthoridJin, DY=7201973614en_HK
dc.identifier.scopusauthoridWong, HL=7402862563en_HK
dc.identifier.scopusauthoridFeng, H=7401736336en_HK
dc.identifier.scopusauthoridWong, YC=7403041798en_HK
dc.identifier.scopusauthoridTsao, SW=7102813116en_HK

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